title: Exercising in a hot environment with muscle damage: effects on acute kidney injury biomarkers and kidney function.
abstract: Unaccustomed strenuous physical exertion in hot environments can result in heat stroke and acute kidney injury (AKI). Both exercise-induced muscle damage and AKI are associated with the release of interleukin-6, but whether muscle damage causes AKI in the heat is unknown. We hypothesized that muscle-damaging exercise, before exercise in the heat, would increase kidney stress. Ten healthy euhydrated men underwent a randomized, crossover trial involving both a 60-min downhill muscle-damaging run (exercise-induced muscle damage; EIMD), and an exercise intensity-matched non-muscle-damaging flat run (CON), in random order separated by 2 wk. Both treatments were followed by heat stress elicited by a 40-min run at 33°C. Urine and blood were sampled at baseline, after treatment, and after subjects ran in the heat. By design, EIMD induced higher plasma creatine kinase and interleukin-6 than CON. EIMD elevated kidney injury biomarkers (e.g., urinary neutrophil gelatinase-associated lipocalin (NGAL) after a run in the heat: EIMD-CON, mean difference [95% CI]: 12 [5, 19] ng/ml) and reduced kidney function (e.g., plasma creatinine after a run in the heat: EIMD-CON, mean difference [95% CI]: 0.2 [0.1, 0.3] mg/dl), where CI is the confidence interval. Plasma interleukin-6 was positively correlated with plasma NGAL (r = 0.9, P = 0.001). Moreover, following EIMD, 5 of 10 participants met AKIN criteria for AKI. Thus for the first time we demonstrate that muscle-damaging exercise before running in the heat results in a greater inflammatory state and kidney stress compared with non-muscle-damaging exercise. Muscle damage should therefore be considered a risk factor for AKI when performing exercise in hot environments.
authors.affiliation: MRCP(UKMRCPE, College of Health and Behavioural Sciences, George Bldg., Bangor Univ., Bangor, Gwynedd, LL57 2PZ, Wales, UK. pepc04@bangor.ac.uk.
authors.forename: Naushad A
authors.initials: NA
authors.lastname: Junglee
authors.forename: Umberto
authors.initials: U
authors.lastname: Di Felice
authors.forename: Alberto
authors.initials: A
authors.lastname: Dolci
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Fortes
authors.forename: Mahdi M
authors.initials: MM
authors.lastname: Jibani
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lemmey
authors.forename: Neil P
authors.initials: NP
authors.lastname: Walsh
authors.forename: Jamie H
authors.initials: JH
authors.lastname: Macdonald
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D015444:Exercise; D018882:Heat Stress Disorders / Q000209:etiology*; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D015850:Interleukin-6 / Q000652:urine; D007668:Kidney / Q000503:physiopathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D009135:Muscular Diseases / Q000209:etiology* / Q000473:pathology; D005082:Physical Exertion; D011518:Proto-Oncogene Proteins / Q000652:urine; D012420:Running / Q000293:injuries; D015854:Up-Regulation
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D015850:Interleukin-6; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D003404:Creatinine
keywords: NGAL protein; exercise; heat stress disorder; inflammation; interleukin-6